Penetration of piperacillin/tazobactam into cancellous and cortical bone tissue

Abstract

Background: The degree of penetration of an antibiotic into the site of infection is an important factor in its therapeutic efficacy, particularly in bone and joint infections. Piperacillin/tazobactam, a β-lactam/β-lactamase inhibitor combination, has been widely used in the treatment of serious infections, including bone infections, but few studies have examined the bone diffusion of these antibiotics. Objective: The purpose of this study was to quantify the bone tissue penetration of piperacillin/tazobactam into cancellous and cortical bone tissue and, from these results, estimate the efficacy of this antibiotic combination against microorganisms commonly encountered in bone infections. Methods: In this open-label, single-arm, noncomparative study, subjects of similar age, body weight, height, and creatinine clearance who were undergoing elective total hip replacement received a single, parenteral 4 g/500 mg dose of piperacillin/tazobactam. Approximately 1.5 hours later, plasma and bone tissue samples were collected and analyzed by a validated high-pressure liquid chromatography method. Results: Twelve patients (3 men and 9 women; mean age, 73.5 years; mean body weight, 52.2 kg) were enrolled. The mean concentrations of piperacillin and tazobactam were 18.9 ± 2.3 μg/g and 2.0 ± 0.3 μg/g, respectively, in cancellous bone tissue and 15.1 ± 2.0 μg/g and 2.0 ± 0.3 μg/g in cortical bone tissue. The bone tissue/plasma ratios for piperacillin and tazobactam were both 0.3 in cancellous bone tissue and 0.2 and 0.3, respectively, in cortical bone tissue. The piperacillin/tazobactam concentration ratio was 9.3:1 in cancellous bone tissue and 7.8:1 in cortical bone tissue. Conclusions: The concentrations achieved in both cancellous and cortical bone tissue were greater than the minimum concentrations required to inhibit the growth of 50% of strains (MIC 50) of most of the susceptible pathogens commonly involved in bone infections.